1. Field of the Invention
The present invention relates to the treatment of abnormal cell growth in the gastrointestinal tract. More particularly, present invention relates to methods, devices and compositions containing hydrophobic photosensitizers for photodynamic therapy for the treatment of unwanted cells and tissues of the intra-anal and perianal region such as anal intraepithelial neoplasia grade III (high grade dysplasia).
2. Invention Disclosure Statement
Anal intraepithelial neoplasia (AIN) or anal dysplasia is an abnormal cell growth in anal tissue that in some cases may progress to cancer. Depending on how the cells look under the microscope, AIN may be further subdivided into AIN Grade I, AIN Grade II and AIN Grade III. The term anal squamous intraepithelial lesions (ASIL) is also used to describe AIN; which can be further classified as low-grade squamous intraepithelial lesions (LSIL) equivalent to AIN I (mild dysplasia), and high-grade squamous intraepithelial lesions (HSIL) which includes AIN II (moderate dysplasia) and AIN III (severe dysplasia). Additionally, the terms anal carcinoma in situ (Stage 0, National Cancer Institute's classification system) and Bowens disease of the anus can also be found in literature, which are sometimes used to denote HSIL. Although LSIL are not thought to be a direct precursor to anal cancer, they may progress to HSIL. On the other hand, HSIL is a progressive, potentially precancerous condition that requires attention; a small proportion of AIN III-type lesions that are not treated or removed may develop into invasive cancer, destroying adjacent tissues and/or organs and ultimately causing death. For this reason it is advantageous to screen for AIN III and treat before it can progress to invasive anal cancer.
To date the management of AIN III lacks accepted treatment protocols. Current treatment modalities for AIN III are electrocautery, cryosurgery and excision but such therapies can result in significant pain or postoperative complications including anal stenosis and severe long-term side effects such as strictures, fecal incontinence and colostomy. Furthermore, ablative treatments are often limited by a high incidence of recurrence. Other treatment options include laser ablation, which can only be used to treat small lesions, and immunomodulation, lacking of sufficient long-term data on therapy results.
In an attempt to provide a method for treating anorectic disorders, Ehrenpreis discloses in U.S. Pat. No. 7,250,445 a method comprising a step of providing a suppository containing between 1000 and 500,000 IU (international units of measure) of an antioxidant selected from the group of Vitamin A, Vitamin C, and Vitamin E; and a step of placing the suppository within rectal cavity for a period of time required for dissolution of the suppository. However, it only provides a substitute or adjunct for conventional treatments for anorectic disorders when no current therapies are available.
Another possible treatment modality, that has the potential for curative treatment of AIN III with less long-term side effects, is PDT. An additional and significant advantage of PDT is that it allows therapeutic illumination of the whole surface of the anal cavity in a single treatment session. This is of importance since other treatment modalities show, based on their high recurrence rates of up to 50%, that it is difficult to determine exactly where to treat for AIN III in the anal cavity.
Photodynamic therapy has been successfully used for superficial, intraluminal and interstitial treatment of (pre) malignant lesions in among others dermatology, esophagus, lungs, head and neck, prostate and vulva. There are a small number of clinical reports on PDT in the anal region for treatment of perianal AIN III and carcinoma in situ using topical or systemic administered ALA. Light delivery for perianal lesions was done using a light delivery device that uses a mirror to direct treatment light onto the treatment area (Hamdan K A, Tait I S, Nadeau V, Padgett M, Carey F, Steele R J; Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy: report of a case; Dis Colon Rectum.; 2003; 46:1555-9). For intra-anal treatment of carcinoma in situ a rectal speculum was used to expose the mucosa. Subsequently a linear diffuser was placed in the center of the speculum for therapeutic illumination. Since the speculum shields half of the tissue two illuminations are necessary where for the second illumination the speculum is rotated 90 degrees (Webber J, Fromm D; Photodynamic therapy for carcinoma in situ of the anus; Arch Surg.; 2004; 139:259-61).
Unfortunately, currently applicators used for PDT of the anal cavity only facilitate the delivery of light to either the perianal or intra-anal region and do not facilitate probes to monitor explicit and/or implicit parameters to provide an insight of the relationship between the treatment and tissue response in situ. Thus, it would be advantageous to dynamically monitor explicit and implicit parameters during perianal or intra-anal PDT treatment in order to aid in optimizing and standardizing PDT therapy.
Due to the disadvantages of conventional treatment modalities and previous PDT therapies of perianal and intra-anal AIN III, there is a need to provide dynamically enhanced PDT treatments for safe and improved clinical PDT treatment protocols.